Rosuvastatin



Better Known as: Crestor

 * Marketed By: AstraZeneca Plc.


 * Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia)


 * Drug Class: HMGR Inhibitor or Statin
 * Date of FDA Approval (Patent Expiration): 2003 (2016)


 * 2009 Sales: $4.5 Billion
 * Importance: Sales of Crestor are the fastest growing among the statins. Statins are so ubiquitous, doctors have even suggested handing them out with fast food. See: the article


 * See Pharmaceutical Drugs for more information about other drugs and disorders

Mechanism of Action
Rosuvastatin is an inhibitor of HMG-CoA Reductase (HMGR), a highly regulated enzyme responsible for the committed step in cholesterol synthesis. Rosuvastatin, like most of the statins, binds HMGR via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Rosuvastatin contribute to binding as well. These interactions help Rosuvastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.

Effectiveness
Rosuvastatin has the greatest efficacy compared to other statins at the same dosage. At 5mg, patients experienced a 40% or greater reduction in LDL as compared to similar results for Atorvastatin at 20mg doses.

Side Effects
Although all of the statins are generally considered safe, rosuvastatin had a higher reported adverse event rate than other statin clinical trials. Typical adverse events include muscle weakness, headache dizziness and slightly increased creatinine kinase (CK) levels (an indication of kidney and smooth muscle damage), although these are common to all the statins (with the exception of elevated CK levels which only occurs in Atorvastatin, Rosuvastatin, and Simvastatin)

Interesting Facts

 * Rosuvastatin has made recent headlines as being nearly equivalent in efficacy to Lipitor, but also cuts the rate of heart attacks and strokes significantly.
 * Unlike other statins, consuming grapefruit juice does not affect the PKs of rosuvastatin.
 * Studies have reveal that that Asians appear to process rosuvastatin differently than members of other races with Cmax and AUC reaching levels which were over 2 fold greater. The FDA has subsequently announced that asians should take half the standard dose to achieve the same cholesterol lowering benefit.

The Jist
The statins are generally viewed as very safe and have been proven effective over the past 15 years. Rosuvastatin is the newest major blockbuster statin and was designed to be taken at lower levels than other statins. Recent studies have indicated rosuvastatin can reduce the likely hood of myocardial infarction and stroke, although this has been refuted by some studies. Truth be told, with major statins like Lipitor coming off patent in the next year or two, pharmaceutical companies are looking for new diseases that can be treated by still-patented statins like Rosuvastatin (Patent expires in 2016). With $4 billion in sales per year and Lipitor going off patent in 2011, resulting in a dramatic price drop in statins as generics flood the market, proving that Rosuvastatin reduces heart attacks, etc. would be worth many billions of dollars. It remains to be seen whether the potential reduction in heart ailments while taking Rosuvastatin, if it exists, can be proven with statistical significance.